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  • Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy #MMPMID32732280
  • Gu H; Chen Q; Yang G; He L; Fan H; Deng YQ; Wang Y; Teng Y; Zhao Z; Cui Y; Li Y; Li XF; Li J; Zhang NN; Yang X; Chen S; Guo Y; Zhao G; Wang X; Luo DY; Wang H; Yang X; Li Y; Han G; He Y; Zhou X; Geng S; Sheng X; Jiang S; Sun S; Qin CF; Zhou Y
  • Science 2020[Sep]; 369 (6511): 1603-1607 PMID32732280show ga
  • The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
  • |*Disease Models, Animal[MESH]
  • |*Mice[MESH]
  • |Administration, Intranasal[MESH]
  • |Animals[MESH]
  • |Betacoronavirus/genetics/*immunology/pathogenicity[MESH]
  • |Coronavirus Infections/immunology/*prevention & control[MESH]
  • |Female[MESH]
  • |High-Throughput Nucleotide Sequencing[MESH]
  • |Humans[MESH]
  • |Immunogenicity, Vaccine[MESH]
  • |Lung Diseases, Interstitial/virology[MESH]
  • |Lung/virology[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Mice, Transgenic[MESH]
  • |Mutation[MESH]
  • |Pandemics/*prevention & control[MESH]
  • |Peptidyl-Dipeptidase A/genetics[MESH]
  • |Pneumonia, Viral/*prevention & control[MESH]
  • |Spike Glycoprotein, Coronavirus/genetics[MESH]
  • |Vaccines, Synthetic/administration & dosage/immunology[MESH]
  • |Viral Vaccines/administration & dosage/*immunology[MESH]
  • |Virulence/genetics[MESH]

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  • suck abstract from ncbi

    1603 6511.369 2020